This renewal application is for the support of a series of radiobiological and dosimetric experiments designed to extend present knowledge of the action of high energy neutrons on hypoxic cells in an effort to answer current questions on the use of high LET radiation in cancer therapy. Sound evidence from basic radiobiological research has already indicated that high LET radiations should be more effective than photon beams in controlling cancers which contain some hypoxic cells. Because of the intense current interest in fast neutron therapy and the unique high energy neutron beam capabilities of the Maryland cyclotron, our experiments to date have been focussed on the radiobiological response to high energy neutrons. We have observed oxygen enhancement ratio (OER) values ranging from 1.2 to 1.5 with high energy neutron beams. These OER values are significantly lower than those obtained from lower energy fast neutron beams or from negative pions, and are comparable to the values expected from heavy ions. The specific objective of the proposed research is to continue investigating (1) the minimum mean neutron energy necessary to bring about significant reductions of OER; (2) the response of additional biological systems; (3) the possibility of depth dependence of OER and RBE. Hard data on these questions should be made available as soon as possible so that the potential advantages of high energy neutron therapy can be considered before large-scale of nationwide commitments are made to any of the possible high LET modalities.